title: The tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in intestinal inflammation.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) associates with the death receptor 3 (DR3) on activated lymphocytes and induces proinflammatory signals. The decoy receptor 3 (DcR3) competes for TL1A binding and inhibits functional signaling. This review focuses on the role of the TL1A/DR3/DcR3 cytokine system in inflammatory bowel diseases (IBDs).
  
  
  RESULTS
  TL1A may induce IFN-γ-mediated and IL-17-mediated proinflammatory pathways in IBDs by acting on DR3-expressing, CD4(+)CD161(+) lymphocytes, which are substantially enriched at the inflamed intestinal mucosa. In addition, TL1A/DR3 signaling results in expansion of the Treg pool with concomitant and transient inhibition of their suppressive function. Constitutive expression of TL1A in transgenic mice was associated with small intestinal inflammation, which was accompanied by colonic fibrosis both spontaneously and under colitogenic conditions. Recent human studies demonstrated that soluble TL1A and DcR3 are present in the systemic circulation in patients with active IBD and decline after successful anti-inflammatory treatment.
  
  
  CONCLUSIONS
  TL1A/DR3 interactions may participate in the pathogenesis of chronic intestinal inflammation and offer novel therapeutic targets for patients with ulcerative colitis and Crohn's disease.
authors.affiliation: aAcademic Department of Gastroenterology, Ethnikon and Kapodistriakon University of Athens, Laikon Hospital, Athens, Greece bDivision of Gastrointestinal and Liver Disease, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Bamias
authors.forename: Li-Guo
authors.initials: LG
authors.lastname: Jia
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D005355:Fibrosis / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15